Rising mortality attributed to agranulocytosis in myeloid leukemia among older adults in the United States : A time trend analysis

Abstract Introduction Agranulocytosis is a life-threatening complication in older adults with myeloid leukemia, yet its population-level mortality burden remains underexplored despite therapeutic advancements. Amidst the aging U.S. population and increasing leukemia incidence, this study examines national mortality trends from 1990 to 2020 to guide hematologic care strategies, supportive interventions and resource distribution. Methods Mortality data were extracted from the CDC WONDER database for the years 1999-2020, using ICD-10 codes related to Myeloid Leukemias (C92.0-C92.9) and Agranulocytosis (D70) as multiple causes of death. Adults aged ≥55 were included. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated and stratified by sex, race, census region, state, and urbanization status. Trends in AAMRs were analyzed using Joinpoint regression software (v5.4.0, National Cancer Institute), and annual percentage change (APC) was computed with 95% confidence intervals (CI) and significance testing. Results Between 1990 and 2020, a total of 5,388 deaths were attributed to agranulocytosis in adults aged ≥55 with myeloid leukemia, with the overall age-adjusted mortality rate (AAMR) showing a consistent upward trend. This increase was significant in both males (APC: +3.07%, p < 0.001) and females (APC: +3.22%, p < 0.001) and among White individuals (APC: +3.27%, p < 0.001). However, mortality estimates for other racial groups could not be extracted due to data unreliability from low case counts. All Census regions demonstrated significantly rising AAMRs (p < 0.001), with the Northeast (APC: +3.51%) and West (APC: +3.34%) exhibiting the steepest increases, followed by the Midwest (APC: +3.20%) and the South (APC: +2.53%). Urbanization-stratified trends showed the steepest rise in Medium Metros, where AAMR increased from 0.31 (2015) to 0.61 (2019), while Large Central Metros maintained consistently high AAMRs (peaking at 0.45). State wise analysis revealed the highest AAMR in Connecticut (0.68) and Rhode Island (0.68), while states including Louisiana (0.15) had among the lowest. Conclusion Agranulocytosis-related mortality in adults aged ≥55 with myeloid leukemias has increased significantly from 1990 to 2020. This trend likely reflects the compounded effect of immunosenescence, hematopoietic insufficiency and regional variability in oncology care. Disproportionately higher and rising AAMRs among Males and White individuals, particularly those residing in the Northeast and West census regions underscores the need for targeted hematologic resource distribution and policy backed geriatric care integration. These findings highlight an urgent need to create tailored strategies prioritizing early identification and optimize supportive care to mitigate treatment-related mortality in this vulnerable population.